Mycobacterium tuberculosis remains one of the leading world health problems despite attempts at modern chemotherapy and vaccination. Tuberculosis is blamed for 2-3 million deaths each year worldwide, and is being diagnosed in increasing measure in developed countries, a phenomenon attributed to the AIDS epidemic. This resurgence of tuberculosis has magnified the need to understand the molecular mechanisms involved in the pathogenesis of M. tuberculosis. M. tuberculosis is a facultative intracellular pathogen that establishes respiratory infection following inhalation of the bacilli into the alveoli of the lungs. The tubercle bacilli establish themselves intracellularly in monocytes, macrophages and reticuloendothelial cells. Cell to cell spread may be accomplished through the lysis of a previously infected host cell. Additionally, the organism is able to survive and grow in the extracellular spaces of lung tissue containing liquefaction residue.
Despite the huge toll in life and resources taken by M. tuberculosis, universally useful vaccines and diagnostic tests for active tuberculosis are currently unavailable. The development of more appropriate candidates is critical, especially with the current rapid spread of the disease world-wide.
Recent studies have implicated the importance of extracellular mycobacterial proteins as virulence factors. By examining the secretion process present in mycobacteria, it may be possible to identify virulence factors that are expressed during human infection and may lead to the development of more effective vaccinations, treatment options as well as a more specific and rapid diagnosis of the disease. In this regard, public protein export has been well characterized in Escherichia coli. Yet, only recently have homologs for several of the Sec factors including SecA have been identified in Gram positive species and now, the Mycobacteria.
The present invention provides the identification of the secA gene from M. tuberculosis. Thus, the development of effective control methods for Mycobacteria is now possible through the identification, isolation, and characterization of the secA gene from M. tuberculosis.